Neuroendocrine Tumors - Types, Signs, Symptoms, Causes, and Treatment

What Are Neuroendocrine Tumors?

Cancers that originate in the neuroendocrine cells, which are cells that are similar to nerve cells (neurons) and hormone-producing cells (endocrine cells), are called neuroendocrine tumors (NETs). These cells make and release hormones when they receive signals from the nervous system. These tumors are rare, and they commonly affect the lungs, small intestine, pancreas, appendix, and rectum. They can grow fast or gradually, and some of these tumors produce excess hormones, resulting in certain symptoms. While other NETs do not release hormones, and even if they do, it is too little to be detected or produce symptoms.

NETs can be benign (not cancerous), while in some tumors, the cells become malignant and spread to other body parts. The symptoms depend on where the tumor is growing, and it’s kind. The doctor will decide the best treatment option for you, depending on the type, location, and the spread of the neuroendocrine tumor. Generally, the doctor can remove or shrink the tumor with the help of therapies, which improves symptoms.

What Are the Types of Neuroendocrine Tumors?

WHO Classification:

1) The World Health Organization categorizes these tumors into:

1. Well-differentiated neuroendocrine tumors - These tumors commonly originate in the digestive tract or lungs, and rarely in the genitourinary tract.

   1. Tumors with benign behavior.

   2. Tumors with uncertain behavior.

2. Well-differentiated (low grade) neuroendocrine carcinomas - These tumors show low-grade malignant behavior.

3. Poorly differentiated (high grade) neuroendocrine carcinomas:

   1. Large cell neuroendocrine carcinomas (LCNEC) - These are aggressive malignant tumors that contain large malignant cells, which show neuroendocrine features.

   2. Small cell neuroendocrine carcinomas (SNEC) - These are extremely rare malignant tumors that commonly affect the lungs.

2) NETs can also be classified into:

1. Carcinoid Tumors - These tumors usually originate in the digestive tract, appendix, lungs, or thymus gland, but can also grow in the brain, gonads, or skin.

2. Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) - NETs that primarily originate in the pancreas. The types include-

   1. Insulinomas - These tumors make insulin, which is the hormone that controls blood sugar levels, and it is the most common type. They are usually not cancerous.

   2. Somatostatinomas - These tumors make somatostatin, which is a chemical that affects the production of other hormones.

   3. VIPomas - These tumors make a chemical required for the release of vasoactive intestinal peptides (VIP). VIP is essential for proper gastrointestinal tract functioning. The majority of VIPomas are malignant.

   4. Glucagonomas - These tumors make glucagon, which is the hormone that raises the blood sugar level. Around 50 % of these tumors are malignant.

   5. Gastrinoma - These tumors make gastrin, which is the hormone that helps digestion. It is usually seen in people with Zollinger-Ellison syndrome. Around 50 % of these tumors are cancerous and spread easily.

3. Medullary Carcinoma - This is the tumor that grows in the cells that release the hormone calcitonin in the thyroid gland. This hormone regulates the levels of calcium in the body.

4. Pheochromocytoma - A rare type of NET that primarily originates in the adrenal gland, which is the gland present above each kidney. These tumors can increase the heart rate and blood pressure by secreting the hormones adrenaline and noradrenaline. These tumors are generally benign.

5. Merkel Cell Carcinoma - It is a neuroendocrine carcinoma of the skin, which grows and spreads quickly to other body parts. It is rare and looks like a bluish-red or flesh-colored nodule, commonly affecting the neck, face, or head.

6. Paraganglioma - It is also a rare tumor that originates in certain nerve cells present throughout the body. These tumors secrete norepinephrine. They are usually slow-growing and benign.

7. Adrenal Cancer - Otherwise called adrenocortical cancer, it is a type of cancer that originates in the adrenal glands. These tumors secrete hormones that practically affect every organ in the body.

3) NETs can also be divided into:

1. Functional Neuroendocrine Tumors - Tumors that produce excess hormones.

2. Nonfunctional Neuroendocrine Tumors - Tumors that do not release hormones or release not enough hormones to produce symptoms.

What Are the Signs and Symptoms of Neuroendocrine Tumors?

NETs do not always cause symptoms in the early stages. Signs and symptoms usually develop due to hormones secreted by these tumors and their location. The common symptoms experienced by patients are:

• Pain due to the tumor growing.

• Tiredness and malaise.

• Unintentional weight loss.

• A lump under the skin.

These tumors can also result in:

• Loss of appetite.

• Bleeding.

• Fever

• Hoarse voice.

• Nausea or vomiting.

• Night sweats.

• Yellowish discoloration of skin or eyes.

The signs and symptoms due to pancreatic NETs include:

• Diarrhea.

• Skin flushing.

• Blurred vision.

• Confusion.

• Increased thirst.

• Increased urination.

• Headache.

• Increased heart rate.

• Dizziness.

• Unusual hunger.

• Tremors.

• Profuse sweating.

The signs and symptoms of carcinoid tumors are:

• Red and itchy skin in the face and neck.

• Cough

• Chest pain.

• Stomachache.

• Trouble breathing.

What Causes Neuroendocrine Tumors?

Doctors do not know the exact cause of NETs, but they have been linked to certain diseases that run in families. When the DNA in neuroendocrine cells mutate, they divide and multiply abnormally, resulting in a tumor. The hereditary conditions that increase the risk of NETs are:

1. Multiple endocrine neoplasia type 1.

2. Neurofibromatosis type 1.

3. Neurofibromatosis.

4. Tuberous sclerosis.

5. Von Hippel-Lindau syndrome.

How Are Neuroendocrine Tumors Diagnosed?

The doctor might perform the following tests and examinations to diagnose NETs:

1. Physical examination - The doctor will palpate swollen lymph nodes or any swellings present under the skin.

2. Blood and urine tests - To check for excess hormones.

3. Imaging tests - You might have to get an ultrasound, CT, or MRI scan to get images of the tumor. Sometimes, positron emission tomography (PET) is used to get detailed images.

4. Biopsy - Here, the doctor will collect a few cells from the tumor by inserting special instruments into the body.

5. Molecular testing - The sample collected during the biopsy is then checked for certain genes or proteins, which will help the doctor decide the treatment.

What Are the Treatment Options for Neuroendocrine Tumors?

The treatment options for NETs are:

1. Surgery - This is the most commonly used treatment option. Benign tumors are completely removed. If that is not possible, the surgeon might remove part or the entire organ that is affected.

2. Radiofrequency Ablation - Here, the doctor will insert a probe into the tumor. This probe produces high-energy radio waves that kill cancer cells.

3. Chemotherapy - The use of drugs to prevent cancer cells from spreading or to kill cancer cells.

4. Cryosurgery - Here, a thin, hollow tube is inserted into the tumor. This tube sends extreme cold to kill the cancer cells.

5. Hormone Therapy - It is commonly used for carcinoid NETs. Here, artificial somatostatin hormone is used to prevent the tumor from producing hormones and resulting in symptoms.

6. Radiation Therapy - The use of high-energy X-rays to destroy cancer cells.

7. Embolization Therapy - This treatment is used to treat NETs in your liver, which cannot be removed surgically. Here, the doctor will inject a substance into the artery that supplies blood to the liver, to block it. This cuts the blood supply to the tumor and the cells start to die.

For more information on neuroendocrine tumors, consult a cancer specialist online now!